Pertussis: Resurgence, Prevention and Role of the Ob/Gyn

Pertussis: Resurgence, Prevention and Role of the Ob/Gyn Kimberly B. Fortner, MD Vanderbilt University Department OB/Gyn Division Maternal-Fetal Medicine Vanderbilt Vaccine Research Program

Learning Objectives At the conclusion of this activity, participants should understand: The epidemiology of pertussis and its recent resurgence in the United States How to diagnose and treat active pertussis infection in an Ob/Gyn population How to prevent pertussis infection in an Ob/Gyn population

Case Study 28yo G5 P0040 uncomplicated pregnancy Received influenza vaccine antenatally Preterm labor at 34 weeks EGA Baby Callie 2 week NICU stay Day of life 36, developed cough Baby Callie with parents

Case Study Parents reassured Day of life 38, returned to pediatrician s office Callie had respiratory arrest Infant died on Day 38 Tdap - Nobody mentioned it...nobody brought it up, nobody talked about it. Rod shaped bacteria (green) lodge in cilia of respiratory tract

Pertussis Highly contagious respiratory infection Outbreaks first described in 16th century 1906 - Bordetella pertussis isolated 1930s - First pertussis vaccine developed 1940s - ~ 200,000 cases/year prior to vaccination

Pertussis Vaccines DTP Vaccine Whole cell Pertussis Diphtheria and Tetanus toxoids Prevents illness in 70-90% children Reactogenic 1 No longer available in US DTaP Vaccine Acellular Pertussis Diphtheria and Tetanus toxoids Acellular vaccine Licensed 1991 Tdap Vaccine Acellular pertussis vaccine Little d and little p Lower quantities of diphtheria and pertussis antigens Adult booster Licensed 2008 1 Edwards KM, Decker MD, Vaccines, 6 th Edition

Cases Pertussis: United States, 1940-2006 250000 1940s widespread DTP vaccination 200000 150000 100000 50000 1991 DTaP licensed in US 0 1940 1950 1960 1970 1980 1990 2000

Cases Pertussis: United States, 1980-30000 2006 25000 20000 15000 10000 1991 DTaP licensed in US 5000 0 1980 1985 1990 1995 2000 2005

Routine DTaP Vaccination Schedule Dose # 1 # 2 # 3 # 4 # 5 Age 2 months 4 months 6 months 12-18 months 4-5 years Minimum Interval --- 4 wks 4 wks 6 mos At school entry So, why are we discussing Pertussis?

Pertussis Epidemic: 2012 Substantial rise in pertussis cases Declared pertussis epidemic Reported cases 2,520 (1300% increase) Highest number cases since 1942

Number of cases Reported NNDSS Pertussis Cases 1922-2011* 300,000 30,000 25,000 250,000 200,000 DTP 20,000 15,000 10,000 5,000 150,000 0 1990 1995 2000 2005 2011* 100,000 50,000 DTaP Tdap 0 1922 1930 1940 1950 1960 1970 1980 1990 2000 2011 * Year *2011 data have not been finalized and are subject to change. 2011 data were accessed on July 5, 2012. SOURCE: CDC, National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System and 1922-1949, passive reports to the Public Health Service

Cases Reported Pertussis by Age Group 30000 25000 20000 1990-2006 <11 11-18 >18 4 5 fold increase in adolescents &adults 15000 10000 5000 0 1990 1993 1996 1999 2002 2005 Year

Why is there a resurgence? Waning immunity Decreased vaccine coverage Better diagnosis Changes in organism Pertussis: Known Villain Aliases: Bordatella; whooping cough

Whole-Cell Pertussis Vaccine Efficacy (%) Waning Vaccine-Induced Immunity 100 80 60 40 20 Observational Studies 1951 1978 1988 Randomized Clinical Trials 0 0 1 2 3 4 5 6 Time Since Last Dose (Years) 1979 1988 Infect Med. 1996;13:S33-S41.

Why Immunity Wanes Natural Infection Prevaccine era = natural boost Postvaccine era = rare boost Large poor of susceptible hosts

Estimated Duration of Immunity Source of Immunity Duration Reference Natural Infection 15 years Wirsing von Konig, 1995 Whole-cell Vaccine UK 6 years Jenkinson, 1988 Finland 6 years He, 1994 Germany 6+ years Lagauer, 2002 Acellular Vaccine Italy 6 years Salmaso et al, 2001 Germany 6+ years Lagauer et al, 2002 Lancet Infect Dis 2002; 2: 744 50

Cycle of Pertussis Susceptibility in Vaccinated Populations Primary Vaccination: Protected Unvaccinated or Partially Vaccinated Infants: Susceptible Booster Vaccination: Prolonged Protection Susceptible Adults and Adolescents: Reservoir of Pertussis No additional booster: Immunity wanes Lancet Infect Dis. 2002;2(12):774.

Cycle of Pertussis Susceptibility in Vaccinated Populations Primary Vaccination: Protected Unvaccinated or Partially Vaccinated Infants: Susceptible Booster Vaccination: Prolonged Protection Susceptible Adults and Adolescents: Reservoir of Pertussis No additional booster: Immunity wanes Lancet Infect Dis. 2002;2(12):774.

Reported Pertussis Outbreaks Adults in the workplace (MMWR 2004; 53(10:216-219) Nursing homes/long-term care facilities (J Inf Dis, 1991/ 164:704-709, JPed 1989; 114:934-939) Students & staff in schools (MMWR, 2003; 52(1)1-4) Health-care workers and hospital patients (Infect Control Hosp Epid 1995; 16:556-563, 2006; 27:546-552, 541-545)

Who is at High Risk for Infection? Unvaccinated Infants Health-care workers Daycare workers Adolescents & adults

Pertussis Incidence Among Infants 2001-2009

Incidence per 100,000 population Pertussis Incidence by Age Group, 300 2011 150 <6 mo 6-12mo 13-18 mo 18-23 mo 2-5 yr 6-9 yr >10 yr AGE GROUP Source: CDC, National Pertussis Surveillance System and Supplemental Pertussis Surveillance System (2012)

Pertussis Deaths in US, 2004-2006 Age at onset <3 mos >3 mos Total 2004 24 3 27 2005 32 7 39 2006 13 3 16 Total 69 13 82 (84%) (16%) CDC, unpublished data, 2007

Unvaccinated Infants with Pertussis: Who is the Source? Infants with documented pertussis infection in GA, IL, MA, MN (PedInfDisJ 2004;23:985-989) Identification of infectious source Other 25% Mother 32% Grandparent 8% Sibling 20% Father 15%

% of Infant Cases Unvaccinated Infant with Pertussis: Age of the Source 60 50 40 30 20 10 0 0-4 5-9 10-19 20+ Age of Source (Years) Ped Inf DisJ 2004;23:985-989

Respiratory Spread Highly infectious Clinical Features Incubation period 7-10 days Insidious onset, similar to minor URI Runny nose Non-specific cough Low-grade fever No sore throat

Classic Whooping Cough Phases Phase 1 Catarrhal Rhinorrhea Conjunctival injection Malaise Low grade fever Lasts 1-2 weeks

Classic Whooping Cough Phases Phase 2 Paroxysmal Bursts of rapid cough with long inspiratory gasp = whoop Lasts 1-6 weeks, as long as 10 weeks 1 1 Hewlett EL Edwards KM. NEJM 2005

Classic Whooping Cough Phases Phase 3 Convalescent Gradual resolution of cough Irritants lead to recurrent coughing Secondary complications

Clinical Picture of Pertussis

Common Clinical Manifestations of Adolescent-Adult Pertussis Cough 3 weeks (97%), cough 9 weeks (52%) Paroxysms 3 weeks (73%) Whoop (69%) Post-tussive emesis (65%) Average missed days of school = 5 Average missed days of work = 7 Average days disrupted sleep = 14 J Infect Dis. 2000;182:174 9.

Common Clinical Manifestations of Infants with Pertussis Minor Complications Subconjunctival hemorrhages, epistaxis, otitis media Major Complications (24%) Pulmonary Neurologic Nutritional Johnston CID 1986; Grant CC, Pediatrics 1998; Mikelova J Pediatr 2003

Diagnosis of Pertussis Nasopharyngeal swab within 2-3 wks of onset Culture Sensitivity 20-80%; Specificity 100% Positive for ~ 2 wks of infection

Diagnosis of Pertussis PCR Limited availability Sensitivity 93.5%; Specificity 97.1% Remains positive for 3-4 wks of infection Serology anti-pt IgG 3-4 weeks after cough Not uniformly available

Treatment of Pertussis Active infection May not decrease symptoms but clears carriage Erythromycin 500mg qid x 14d TMP-SMX DS bid x 14 d Azithromycin 500mg x 1d. 250mg qd x 4d Post-exposure prophylaxis Within 3 weeks if close contact = within 3 feet or in close space Same as treatment regimen MMWR 2008; 57(RR4): 10

Pertussis is... Common Morbid Difficult to diagnose Contagious Very bad for infants A vaccine-preventable disease!

Vaccines aren t just for kids anymore!

2009 ACIP/AAP Recommendations Adolescents age 11-18 = single booster dose of Tdap instead of Td (June 2005) Adults age 19-64 = Tdap in place of their next decennial Td (October 2005) MMWR 2009; 57(53)

2009 ACIP: Pregnant & Postpartum Women Women of childbearing age should receive Tdap in place of their next decennial Td but ideally during preconception wellness Pregnant women should receive Tdap postpartum before leaving hospital if last Td > 2 yrs Non-pregnant adolescents and adults having direct contact with an infant (< 1 yr) should receive Tdap at least 2 wks before contact if last Td > 2 yrs MMWR 57 (04); 1-47, 51 MMWR 2009; 57(53)

Cocooning Immunization Strategy 2008-2011, CDC-ACIP recommended strategy of cocooning vaccination

Issues with Cocooning Strategy Limited recall last Td Ob/Gyns, L&D RNs, and Hospitals not prepared Inability vaccinate household contacts Postpartum vaccination fails to leverage potential for passive immunity

Interval since last Td Mass vaccination campaign of healthcare workers 4524 vaccinated, 2221 (49.1%) completed survey Comparison of adverse events/reactogenicity Vaccine 28 (2010) 8001 8007

Interval since last Td < 2 yrs last Td n = 97 2 yrs last Td n = 578 Pain 67.9% 73.5% Redness* 23.5% 19.6% Swelling* 37.8% 33.4% Subjective fever* 15.2% 11.4% No difference in moderate to severe symptoms No difference in serious adverse events 16 pregnant women vaccinated all normal outcomes Vaccine 28 (2010) 8001 8007

Tdap during pregnancy 104 women 52 received Tdap prior or during pregnancy 52 received Tdap postpartum Maternal and cord blood collected Findings: Higher cord blood antibodies if vaccinated in pregnancy High correlation between maternal and cord blood antibody levels Gall SA, Am J Obstet Gynecol 2011;204:334.e1-5.

Safety of Tdap in Pregnancy Tdap vs Td vaccine during pregnancy 440 pregnant women and their infants Compared antibody levels: birth, 2, 4, 6, 7, 12, and 13 months of age Safety of Tdap in pregnancy: obstetric outcomes and developmental assessment at 1 year Halperin SA, NCT00553228

Pertussis Vaccine in Healthy Pregnant Women Double-blind, crossover RCT Pregnant women randomized 2:1 to Tdap during pregnancy vs. postpartum Antibody levels at birth, 2, 7, and 13 months Developmental assessment at 13 months NCT00707148 - NIAID

Updated and Provisional ACIP Recommendations Tdap can be administered regardless of interval since last Td Tdap should be given in 2 nd or 3 rd trimester in women without prior Tdap Continue Tdap vaccination for household contacts of infants ACIP Meeting June 22, 2011 http://www.cdc.gov/vaccines/recs/provisional/default.htm

Tdap Vaccination Summary As of August 2011, Tdap Vaccination is recommended for pregnant women in the late second (>20 weeks) or third trimester who have not previously received Tdap. If not given during pregnancy, Tdap should be given postpartum.

Newest ACIP Guidelines October 2012 Vaccination with EACH Pregnancy Review of Available Data

Pertussis Who should advocate for patients to be vaccinated? ALL OF US! 1 Jamieson DJ et al. Lancet 2009;374:451-8.

Ob/Gyn s Role in Immunization Often first medical contact for young women Provide 1 / 3 of medical visits for women ages 17 21 Function as primary care practitioners Caring for pregnant women

Ob/Gyn s Role in Immunization Pediatricians & Ob/Gyns -near eradication of congenital rubella Remarkable achievement = Rh Isoimmunization (1968) 1973 over 50,000 babies lives saved Time magazine Top Ten Medical Achievements of the 1960 s

Who benefits from maternal immunization? Pregnant woman Family/Household contacts Fetus/Infant

NIH s Network of Vaccine and Treatment Evaluation Units (VTEUs)

How does Vanderbilt Help me?

We have seen the Enemy Pertussis VTEU Study Objectives To evaluate longevity of vaccination protection To understand pertussis antibody levels in human breast milk Pertussis: Known Villain Aliases: Bordatella; whooping cough

Ongoing studies Enrolling 55 women Post partum Healthy Full term delivery No Tdap in 2 years prior

Thank you!